Angiopoietin-2 Inhibition Rescues Arteriovenous Malformation in a Smad4 Hereditary Hemorrhagic Telangiectasia Mouse Model.

Our studies provide a novel mechanism whereby loss of Smad4 causes increased Angpt2 transcription in ECs leading to AVM formation, increased blood vessel calibers and changes in EC morphology in the retina. Blockade of ANGPT2 function in an in vivo Smad4 model of HHT alleviated these vascular phenotypes further implicating ANGPT2 as an important TGFβ downstream mediator of AVM formation. Therefore, alternative approaches that target ANGPT2 function may have therapeutic value for the alleviation of HHT symptoms, such as AVMs.